The specific aim of the proposed study is to evaluate the efficacy of a novel AIDS therapeutic, PPB2, when compared with the natural progression of disease in the pathogenic SHIV-229 macaque model system. Human immunodeficiency virus (HIV) infection and the progression to AIDS have challenged the scientific community for nearly two decades. Most of the anti-HIV drugs in use today reduce the level of free virus during treatment, but the number of virus-infected cells is not substantially affected. Therefore, virus-infected cells and the virus reservoir in infected tissues are major deficiencies of current therapy. The rapid appearance of HIV mutants with drug resistance is the other major challenge to clinical treatment of HIV infection. Because of these problems, there is an urgent need to continually investigate new therapeutics, particularly those with alternate mechanisms of action. This project will evaluate compounds that appear to exert their effects through i nteraction s with host cells, interfering with viral replication and/or establishing an effective anti-HIV immune response. We saw promising results with PPB2 in macaques chronically infected with our highly pathogenic SHIV-229. We are now expanding on these data and adding the complementary observations from a group of control (non-treated) animals. FUNDING NIH grant RR00166 and a contract with Hollis Eden Pharmaceuticals.